Heterocyclic phosphorus-containing monofluorides and process for making same



2 922,813 HETEROCYCLIC PnosPnoRUs CONTAINING MONOFLUORIDES AND PROCESSFOR MAK- ING SAME William M. Lanham, Charleston, W. Va., assignor toUnion Carbide Corporation, a corporation of New York No Drawing.Application April 10, 1957 Serial No. 651,834 9 Claims. (Cl. 260461)wherein X is oxygen or sulfur, and each of R, R, R R and R designates aradical of the class consisting of hydrogen and the alkyl radicals.Preferably each R, R and R represents hydrogen or a lower alkyl radicalhaving 1 to 6 carbon atoms, and each R and R respectively, representshydrogen or an alkyl radical having 1 to 20 carbon atoms.

The novel compounds of the invention are effective insecticides, havingspecial utility for the control of such insect pests as bean aphids(Aphis rumicis) and red spider mites (T etranychus bimaculatus). Thecompounds also have prospective utility as fungicides and bactericidesand may be useful in war gases, alone or in conjunction with the highlyeffective diisopropyl fluorophosphate. (See Chemical Reviews, vol. 48,No. 2, pages 225-254.)

According to the invention, these novel compounds can be made by variousprocesses herein described. Thus, they can be made by reacting aZ-chloro-Z- oxo derivative of a 1,3,2-dioxaphosphorinane or of acorresponding 2- chloro-Z-thiono derivative thereof, having thestructure wherein R, R, R R R and X have the meanings hereinbeforeindicated, with an alkali metal or ammonium salt of hydrofluoric acid,at temperatures Within the range from around 25 C. to around 120 C. orhigher, pref erably in the presencev of an inert solvent for thephosphorus-containing reactant and the desired product. Among solventssuitable for use in the process are benzene, toluene, the xylenes,carbon tetrachloride, ethylene dichloride, heptane, hexane, anddimethylformamide.

' The reaction temperature selected for use depends upon the choice ofmetal fluoride and solvent used, since certain solvent-fluoridecombinations are more effective than others. Thus, although the reactionis very sluggish at 120 C. when sodium fluoride and toluene are used,the reaction occurs very readily at 70-120 C. when potassium fluorideand dimethylformamide are employed. The same reaction is readilyconducted at 25 C. when ammonium fluoride and dimethylformamide areused, and at 70 C. when benzene is used with the same fluoride.

Although it is preferred that the fluoride reactant em ployed in theprocess be essentially anhydrous, the hydrated salts can be used.

The process involves the reaction of equimolar quantities of thephosphorus-containing compound and the alkali metal fluoride or ammoniumfluoride. However, an excess of the fluoride is preferred. Usually aexcess is employed, although a slight excess (5% to 10% mol) issuflicient.

The novel compounds also can be prepared by'reacting alkali metalbifluorides or ammonium bifluoride with a pyrophosphate orpyrothiophosphate compound having a structure corresponding to theformula R\ /R R oo x ll 12 (|JH0 R 2 wherein X is oxygen or sulfur, andR, R, R R and R respectively, designates a radical of the classconsisting of hydrogen and the alkyl groups. This reaction is conductedat temperatures within the range from around 25 C. to around C. orhigher, and preferably in the presence of an inert solvent of the kindhereinbefore described. In this form of the invention the reaction whichoccurs can be illustrated by the equation: 7 if it 0 O O wherein Grepresents the hydrocarbon residue of a 1,3-- alkanediol, .X representsoxygen or sulfur, and M represents an alkali metal or ammonium radical.

The 2-chloro-2-oxo-1,3,2-dioxaphosphorinane starting materials can bemade by reacting a 1,3-alkanediol Withphosphoryl chloride in aboutequimolar proportions, at temperatures around 10 to 25 C., as disclosedin applicants copending application, Serial No. 340,400, filed March 4,1953. g

The 2-chloro-2-thiono 1,3,2-dioxaphosphorinane reactants can be made byreacting a 1,3-alkanediol with thiophosphoryl chloride in the presenceof a hydrogen chloride sequestering agent, as described in applicantsco-. pending application, Serial No. 414,497, filed March 5, 1954.

The heterocyclic pyro compounds used as starting materialsin one form ofprocess can be made by reacting a2-chloro-2-oxo-1,3,2-dioxaphosphorinane with a salt of a saturatedaliphatic carboxylic acid, at temperatures.

around 50 C. to 200 C., as disclosed in applicants copendingapplication, Serial No.'388,681, filed October 27, 1953. a

The novel products of the invention are readily recovered from thereaction mixture by treatment thereof with a solvent for the "aforesaidproducts. The latter then can be purified by vacuum distillation or bycrystallization from the solvent, as hereinafter disclosed in theaccompanying examples illustrating the invention.

Other representative products of this invention include: 5 butyl 5ethyl-Z-fluoro-Z-oxo-l,3,2-dioxaphosphori nane; 5,5diethyl-2-fluoro-2-thiono-1,3,2-dioxaphosphorinane; 5 ethyl2-fluoro-2-thiono-1,3,2-dioxaphosphorinane; 2 fluoro4-methy1-2-thiono-l,3,2-dioxaphosphori-" nane; 2 fluoro4-methyl-2-oxo,1,3,2-dioxaphosphori-' nane; 2 fluoro4,6-dimethyl-2-oxo-1,3,2-dioxaphos-- ,phorinane; 2 fluoro4,6-dimethyl-2-thiono-1,3,2-di-" oxaphosphorinane; and the 4-ethyl-,4-butyl-, 4-(l-ethylpentyl), 4-tridecyl-, -decyl-, 5-heptadecyl-,4-methyl-5- ethyl-, 4,5-dibutyl-, 4-propyl-5-tetradecyl-, 5,5-dibutyl-,5=butyl-5-dodecyl-, 4-ethyl-4,6-dimethyl-, and4,4,5-,5-tetramethyl-substituted Z-fluoro-Z-oxo-1,3,2-dioxaphosphorinanes and the corresponding2-flu'oro-2-thiono-1,3,2-dioxaphosphorinanes.

a Example 1 A solution of 212 grams (1 mol) of 2-chloro-5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinane and 50 cc. of benzene were addeddropwise to an agitated suspension of 74 grams (2 mols) of anhydrousammonium fluoride in 500 cc. of benzene during 40 minutes whilemaintaining the reaction mixture at 70 C. After an additional 4 hours at70 C. and standing overnight at 25 C., the reaction mixture wasfiltered, and the filtrate was stripped by distillation to a kettletemperature of 60 C. under less than 2 mm. of mercury pressure. Thewhite crystalline residue was recrystallized from ethyl ether bydissolving in 300 cc. of the ether, cooling to -35 C., filtering, anddrying at 25 C. under 2 mm. of mercury pressure. The 180 grams of whiteproduct recovered had the following properties: melting point=3539 C.;percent purity (by saponification)=97.8; percent P=16.22 (theory=15.79);percent 'F=9.47 (thcory=9.68); percent C=43.3l (theory=42.87); percentH=7.43 (theory =7.19); percent yield=92.

' can, om-o o 0 \ll C1115 CHi-O A 95100% control of bean aphids onnasturtium plants infested therewith was. secured in 24 hours byspraying the plants with an aqueous solution containing 0.125 gram ofthis compound per 100 cc. of said solution.

' Example 2 A suspension consisting of 26 grams (0.7 mol) of ammoniumfluoride in 300 cc. of dimethylformamide and 47 grams (0.206 mol) of2-chloro-5,S-diethyI-Z-thionol,3,2'dioxaphosphorinane was heated at 70C. for 4 a stripped by distillation at 60 ing point of -37.5

hours, filtered, and the residue was washed with ethyl ether. Thefiltrate and ether washings were combined and stripped by distillationto a temperature of 60 C. under 5 mm. of mercury pressure. The resultantfluid residue was dissolved in ethyl ether, washed with water, and theether solution dried over calcium sulfate and stripped by distillationto a temperature of 40 C. under less than 5 mm. of mercury pressure. Thewhite crystallind residue was recrystallized from ethyl ether at --30 C.and stripped by distillation at 25 C. under 5 mm. of mercury. Theresultant white solid had the following properties: melting point=33340.; percent yield=54%; percent Cl==nil; percent 1 :14.91 (theory=14.59);percent F=8.59 (theory=8.95); percent S=14.90 (theory=15.10); percentC=39.55 (theory =39.6); percent H=6.90 (theory=6.65).

Example 3 To an agitated suspension of 1 mol of ammonium fluoride in 300cc. of benzene maintained at 70 C. there were added dropwise during 20minutes 0.05 mol of 2- chloro2-oxo-4,4,6-tri.methyl-l,3,2-dioxaphosphorinane. After an additional 6hours at 70 C. the reaction mixture was filtered, the filtrate strippedby distillation at 40 C. under less than 2 mm. of pressure, and theresidue was dissolved in ethyl ether, crystallized therefrom at 30 C.,and the residual solvent stripped by distillation at 25 C. at 2 mm.pressure. The residual white fluffy solid product had a melting point of38941 C-;

and the following analysis, by weight: percent P: 17.17 (theory=l7.01);percent F; 10.46 (theory=10.43); percent C=39.23 (theory=39.59); percentH=6.77 (theory =6.64); percent purity (by saponification) =98.1; percentyield=55.

I CH-O o Example 4 A suspension of 2 mols of potassium fluoride in one 7mol of 2-chloro-5,5-diethyl-2-oxo-1,3,2-dioxaphosphorinane and 500 cc.of dimethylformarnide was heated for 4 hours at a kettle temperature of70-120 C. Subsequently, the reaction mixture was filtered, and thefiltrate C. under 2 mm. of mercury pressure. The residue was dissolvedin 300 cc. of ethyl ether and washed with ice water at +10 C. The ethersolution then was stripped by distillation at C. under 2 mm. pressure,and the white solid residue was purified by recrystallization bydissolving in ethyl ether, cooling to 0 C. and filtering. The residualethyl ether was stripped from the residue by distillation at 30 C. under2 mm. pressure yielding 5,S-diethyl-Z-fiuoro-Z-oxo-1,3,2-dioxaphosphorinane as a white fiufiy solid having a melt C.; a percentpurity (by saponification) of 99.8% and the following analysis (byweight): percent P=l5.48 (theory=15.79); percent '-F=9.37 (theory=9.68);percent C=43.30 (theory=42.87); percent H=7.43 (theory=7.l9); percentyield=42.

Example 5 A suspension consisting of 2 mols of potassium fluoride in onemol of 2-ch1oro-5-ethyl-2-oxo-4-propyl-1,3,2-dioxaphosphon'nane and 500cc. of dimethylformamide was heated at 70 l20 C. for 4 hours. Afterstanding overnight at 25 C., the reaction mixture was filtered, thefiltrate stripped by distillation at 60 C. under a pressure of less than2 mm. of mercury, and the residual product was dissolved in ethyl ether,washed with water at 10 C., and the washed ether solution was strippedby distillation at 60 C. under less than 2 mm. of mercury. The residuallight yellow liquid residue was distilled on a falling film type ofmolecular still at C. under less than 0.2 mm. of mercury, yielding5-ethyl-2-fiuoro-2-oxo-4-propyl-l,3,2- dioxaphosphorinane in the form ofa clear, colorless distillate having the following properties: percentpurity (by saponification) =96.5; n =1.43l0; percent P: 14.25

(theory=14.73); percent F=8.76 (theory=9.03); per

phorinane was secured. The product was somewhat purer than that securedin Example 1 and had the following properties: Melting point=36-39 C.;percent purity (by saponification)=99.9%; percent P=l6.46 (theory=l5.79); percent F=9.84 (theory=9.68); percent C =43.06 (theory=42.87);percent H=7.45 (theory =7.19); percent yield=51.

Example 7 To an agitated suspension of 68 grams (1.2 mols) of ammoniumbifluoride in 200 cc. of benzene held at 70 C. there were added dropwiseduring 30 minutes 84 grams (0.227 mol) of2,2'-dioxo-5,5,5',5'-tetraethylpyro-1,3,2-dioxaphosphorinane dissolvedin 400 cc. of benzene. After heating an additional 12 hours at 70 C. thereaction mixture was washed three times with water, then with diluteaqueous sodium bicarbonate, and then again with water until neutraltoward litmus. The benzene solution then was dried over calcium sulfate,filtered, and the filtrate stripped by distillation at 55 C. under apressure of less than 2 mm. of mercury. The residual white solid productwas purified by recrystallization from ethyl ether by dissolv' g it in100 cc. of ethyl ether, cooling to 20 C., filtering, and stripping theresidue thus obtained at 25 C. under 2 mm. of mercury pressure. The 18grams of 5,5-diethyl-2-fluoro-2-oxo-1,3,2- dioxaphosphorinane wassecured as a white solid residue having the following properties:percent purity (by saponification) =99%; melting point=36-39 C.; percentyield=40; analysis, by weight, percent P=16.05; percent =9.94; percentC=42.86; percent H=7.24.

The by-product acid of the principal reaction is converted to thewater-soluble sodium salt of the acid by the sodium bicarbonatetreatment, and this salt is removed by the subsequent washing withwater.

This application is a continuation-in-part of my pending application,Serial No. 417,505, filed March 19, 1954.

The invention is susceptible of modification within the scope of theappended claims.

What is claimed is:

1. As new compounds, heterocyclic fluorineand phosphorus-containingcompounds having structures corresponding to the formula wherein X isselected from the class consisting of oxygen and sulfur; each R, R and Rrespectively, is a member of the class consisting of hydrogen and thelower alkyl radicals having 1 to 6 carbon atoms; and each R and Rrespectively, represents a member of the class consisting of hydrogenand the alkyl radicals having 1 to 20 carbon atoms.

2. As new compounds, 2-fluoro-2-oxo-1,3,2-dioxaphosphorinanessubstituted on at least one of the ring carbon atoms with at least onelower alkyl group, said compounds being otherwise unsubstituted.

3. As new compounds, 2-fluoro-2-oxo-1,3,2-dioxaphosphorinanessubstituted on the ring carbon atom in the 5-position by two lower alkylgroups, said compounds being otherwise unsubstituted.

4. As new compounds, 2-fluoro-2-thiono-1,3,2-dioxaphosphorinanessubstituted on at least one of the ring carbon atoms with at least onelower alkyl group, said compounds being otherwise unsubstituted.

5. As new compounds, 2-fluoro-2-thiono-1,3,2-dioxaphosphorinanessubstituted on the ring carbon atoms in the 5-position of thedioxaphosphorinane ring by two lower alkyl groups, said compounds beingotherwise unsubstituted.

6. As a new compound, 2-fluoro-2-oxo-l,3,2-dioxaphosphor-inane.

7. As a new compound, 2-fluoro-2-thiono-1,3,2-dioxaphosphorinane.

8. Process for making heterocyclic fluorineand phosphorus-containingcompounds, which comprises reacting a fluoride selected from the classconsisting of the alkali metal fluorides and ammonium fluoride with acompound having the structure:

wherein X designates a member of the class consisting of oxygen andsulfur, each R, R and R respectively, designates a member of the classconsisting of hydrogen and the alkyl radicals having 1 to 6 carbonatoms, and R and R respectively, designates a member of the classconsisting of hydrogen and the alkyl radicals having l to 20 carbonatoms, in the presence of an inert solvent for the phosphorus-containingcompound, and recovering from the resultant reaction mixture a compoundof the wherein X, R, R, designations.

9. Process for making heterocyclic fluorineand phosphorus-containingcompounds, which comprises reacting a b' uoride selected from the classconsisting of the alkali metal and ammonium bifluorides with a compoundhaving the structure:

R, R and R have the aforesaid from the resultant reaction mixture acompound of the formula:

R R o -o r *1 f 3 011-0 wherein X, R, R, R R and R have the aforesaiddesignations.

References Cited in the file of this patent UNITED STATES PATENTS2,409,039 Hardy et a1. Oct. 8, 1946 2,661,365 Gamrath et a1. Dec. 1,1953 2,744,128 Morris et al. May 1, 1956 OTHER REFERENCES McCombie etal.: Nature, 157, 287-289 (1946). Sartori: Chem. Rev., 48, 225 and245-254 (1951). Mitchell et al.: I. Am. Chem. Soc., 72, 5779 (1950).

UNITED STATES PATEN OFFICE CERTIFICATE OF COIRECTION Patent Noe232224313 January 26V 1960 William M, Lznha m It is hereby certifiedthat erro appears in the printed specification of the above numberedntent requiring correction and that tle said Letters Patent ShOlid readas corrected belowa line 67 for "Oo05 moi' read 0.5 mol Columl 3,

Signec and sealed this 5th day f July (SEAL) Attest:

KARL H. AXINE AttestingOflcer ROBERT C. WATSON Comnissioner of Patents

1. AS NEW COMPOUNDS, HETEROCYCLIC FLUORINE-AND PHOSPHOROUS-CONTAININGCOMPOUNDS HAVING STRUCTURES CORRESPONDING TO THE FORMULA
 8. PROCESS FORMAKING HETEROCYCLIC FLUORINE-AND PHOSPHOROUS-CONTAINING COMPOUNDS, WHICHCOMPRISES REACTING A FLUORIDE SELECTED FROM THE CLASS CONSISTING OF THEALKALI METAL FLUORIDES AND AMMONIUM FLUORIDE WITH A COMPOUND HAVING THESTRUCTURE
 9. PROCESS FOR MAKING HETEROCYCLIC FLUORINE- ANDPHOSPHORUS-CONTAINING COMPOUNDS, WHICH COMPRISES REACTING A BIFILUORIDESELECTED FROM THE CLASS CONSISTING OF THE ALKALI METAL AND AMMONIUMBIFILUORIDES WITH A COMPOUND HAVING THE STRUCTURE: